Lisa Wood, PhD

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The long-range goal of our research is to effectively treat and manage the most common symptom experienced by cancer patients undergoing chemotherapy, radiation therapy or both; fatigue.

In contrast to fatigue in a healthy person, the fatigue experienced by the cancer patient undergoing treatment is chronic and distressing and is unlikely to be relieved by rest. Cancer treatment related fatigue (CTRF) has a profound negative impact on physical functioning, quality of life (QOL) and the patient’s ability to receive the prescribed treatment.

Some patients do not complete treatment because of CTRF while others experience fatigue-related treatment delays or dose reductions. We hypothesize that treatment induced inflammatory cytokine production plays an important etiological role in CTRF. There are several lines of evidence that support our hypothesis.

First, in addition to fatigue, cancer patients undergoing treatment often experience several other symptoms including anorexia, cachexia, pain, sleep disturbance, depression, and anemia, which can impact the subjective sensation of fatigue. There is now considerable evidence generated in animal models and in clinical populations that the inflammatory cytokines IL-1b, TNF-a and IL-6 play a significant role in the etiology of these symptoms. In this regard CTRF may be homologous to sickness behavior, a normal response to infection or tissue injury. The peripheral production of interleukin-1 (IL-1b), tumor necrosis factor alpha (TNF-a) and interleukin-6 (IL-6) triggers their production in the central nervous system (CNS) and many of the behavioral consequences of sickness behavior are mediated by their action or production within the CNS.

Second, mechanistically distinct cytotoxic systemic antineoplastic agents and whole body or localized radiation have been shown to induce the production of inflammatory cytokines both in experimental systems and in clinical populations. Third, fatigue is a common symptom in chronic inflammatory conditions such as rheumatoid arthritis and treatment with cytokine blockers can reduce fatigue levels associated with these conditions.

To date the molecular mechanisms underlying the initiation and perpetuation of CTRF are not well established, and, the precise role of inflammatory cytokines, if any, in CTRF remains unclear. Our research program utilizes a pre-clinical and clinical approach to examine the relationship between cancer treatment, inflammatory cytokines and CTRF. This “bench to bedside” approach to understanding the cause of CTRF arises from a unique interdisciplinary collaboration among molecular, behavioral, and clinical investigators all working at various points within the spectrum of cancer research at our institution and hence, represents a major innovation in cancer symptom research.

Understanding whether CTRF is initiated by the production of IL-1b, TNF-a, and IL-6 may lead to new treatment strategies, that will improve physical functioning, QOL and the patient’s ability to receive the prescribed treatment.

Current Grant Funding:

The Role of Cytokine Deregulation in Cancer Treatment Related Fatigue: Our long-range goal of this program of research is to develop targeted therapies to effectively treat and manage cancer related symptoms, including fatigue. To this end, we have developed an innovative murine model to experimentally evaluate the associations among cancer and its treatment.